ArticleJCI insight2020
TrkB agonists prevent postischemic emergence of refractory neonatal seizures in mice.
Article in JCI insight, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
13 citing papers in PubMed, 24 citations in OpenAlex.
- Plasma KCC2, NKCC1, and GABA as peripheral biomarkers in autism spectrum disorder: a combined ROC analysis.Metabolic brain disease · 2026Article
- BDNF in ventrolateral orbitofrontal cortex to dorsolateral striatum circuit moderates alcohol consumption, seeking and relapse.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Unlocking Alzheimer's Disease: The Role of BDNF Signaling in Neuropathology and Treatment.Neuromolecular medicine · 2025Review
- The Possible Role of Brain-derived Neurotrophic Factor in Epilepsy.Neurochemical research · 2024Review
- Intranasal Administration of BDNF Improves Recovery and Promotes Neural Plasticity in a Neonatal Mouse Model of Hypoxic Ischemia.Experimental neurobiology · 2024Article
- Neuronal KActa pharmacologica Sinica · 2024Review
- Factors not considered in the study of drug-resistant epilepsy: Psychiatric comorbidities, age, and gender.Epilepsia open · 2022Review
- Chronic partial TrkB activation reduces seizures and mortality in a mouse model of Dravet syndrome.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Discovery of Small Molecule KCC2 Potentiators Which AttenuateFrontiers in cell and developmental biology · 2022Article
- Targeting ischemia-induced KCC2 hypofunction rescues refractory neonatal seizures and mitigates epileptogenesis in a mouse model.Science signaling · 2021Article
- Novel Therapeutics for Neonatal Seizures.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2021Review
- Novel Concepts for the Role of Chloride Cotransporters in Refractory Seizures.Aging and disease · 2021Review
- Brain-Derived Neurotrophic Factor in Neonatal Seizures.Pediatric neurology · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Refractory neonatal seizures do not respond to first-line antiseizure medications like phenobarbital (PB), a positive allosteric modulator for GABAA receptors. GABAA receptor-mediated inhibition is dependent upon electroneutral cation-chloride transporter KCC2, which mediates neuronal chloride extrusion and its age-dependent increase and postnatally shifts GABAergic signaling from depolarizing to hyperpolarizing. Brain-derived neurotropic factor-tyrosine receptor kinase B activation (BDNF-TrkB activation) after excitotoxic injury recruits downstream targets like PLCγ1, leading to KCC2 hypofunction. Here, the antiseizure efficacy of TrkB agonists LM22A-4, HIOC, and deoxygedunin (DG) on PB-refractory seizures and postischemic TrkB pathway activation was investigated in a mouse model (CD-1, P7) of refractory neonatal seizures. LM, a BDNF loop II mimetic, rescued PB-refractory seizures in a sexually dimorphic manner. Efficacy was associated with a substantial reduction in the postischemic phosphorylation of TrkB at Y816, a site known to mediate postischemic KCC2 hypofunction via PLCγ1 activation. LM rescued ischemia-induced phospho-KCC2-S940 dephosphorylation, preserving its membrane stability. Full TrkB agonists HIOC and DG similarly rescued PB refractoriness. Chemogenetic inactivation of TrkB substantially reduced postischemic neonatal seizure burdens at P7. Sex differences identified in developmental expression profiles of TrkB and KCC2 may underlie the sexually dimorphic efficacy of LM. These results support a potentially novel role for the TrkB receptor in the emergence of age-dependent refractory neonatal seizures.
Indexed as
Identifiers
What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.